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Stratification of clear cell renal cell carcinoma by signaling pathway analysis

  • Mattia Cremona
  • , Virginia Espina
  • , Dario Caccia
  • , Silvia Veneroni
  • , Maurizio Colecchia
  • , Mariaelena Pierobon
  • , Jianghong Deng
  • , Claudius Mueller
  • , Giuseppe Procopio
  • , Cinzia Lanzi
  • , Maria Grazia Daidone
  • , William C.S. Cho
  • , Emanuel F. Petricoin
  • , Lance Liotta
  • , Italia Bongarzone*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Investigation of cell signaling pathways in 16 clear cell renal cell carcinomas to identify groups based on commonly shared phosphorylation-driven signaling networks. Using laser capture microdissection and reverse-phase protein arrays, we profiled 75 key nodes spanning signaling pathways important in tumorigenesis. Analysis revealed significantly different (P < 0.05) signaling levels for 27 nodes between two groups of samples, designated A (4 samples; high EGFR, RET, and RASGFR1 levels, converging to activate AKT/mTOR) and B (12 samples; high ERK1/2 and STAT phosphorylation). Group B was further partitioned into groups C (7 samples; elevated expression of LC3B) and D (5 samples; activation of Src and STAT). Network analysis indicated that group A was characterized by signaling pathways related to cell cycle and proliferation, and group B by pathways related to cell death and survival. Homogeneous clear cell renal cell carcinomas could be stratified into at least two major functional groups.

Original languageEnglish
Pages (from-to)237-249
Number of pages13
JournalExpert Review of Proteomics
Volume11
Issue number2
DOIs
StatePublished - Apr 2014
Externally publishedYes

Keywords

  • HIF
  • autophagy
  • hypoxia
  • mTOR
  • renal cell carcinoma
  • reverse-phase protein array
  • signaling Putative biomarkers andpathway

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